Can I take gabapentin, clonidine, Valium (diazepam) and Abilify (aripiprazole) together?

Can You Take Gabapentin, Clonidine, Valium, and Abilify Together?

Yes, you can take these medications together, but this combination requires careful monitoring due to significant additive central nervous system (CNS) depression and cardiovascular risks, particularly from combining benzodiazepines (Valium) with gabapentin and clonidine.

Critical Safety Concerns

Benzodiazepine and Gabapentin Combination

• The 2019 American Geriatrics Society Beers Criteria specifically warns against combining opioids with gabapentinoids, and this caution extends to other CNS depressants including benzodiazepines 1
• Concurrent use of benzodiazepines with gabapentin increases fall risk and CNS depression 1
• The combination of three or more CNS agents (which would include Valium, gabapentin, and potentially clonidine) significantly increases fall risk 1

Benzodiazepine Risks

• The FDA has issued a black box warning about combining benzodiazepines with other sedating medications, warning of possible serious effects including slowed or difficult breathing and death 1
• Benzodiazepines should be avoided whenever possible when patients are on other CNS depressants 1
• Concurrent benzodiazepine use with other CNS depressants is associated with a near quadrupling of overdose risk 1

Clonidine-Specific Considerations

• Clonidine commonly causes sedation, hypotension, and bradycardia 1
• When combined with other sedating medications, clonidine's cardiovascular effects (bradycardia and hypotension) may be enhanced 1
• Aripiprazole (Abilify) can enhance the hypotensive effects of clonidine due to its alpha-adrenergic antagonism 2

Aripiprazole Drug Interactions

• Aripiprazole has documented interactions with benzodiazepines: the combination of aripiprazole and lorazepam (a benzodiazepine like Valium) produces greater sedation and orthostatic hypotension than either drug alone 2
• Blood pressure and sedation must be monitored when combining aripiprazole with benzodiazepines 2

Clinical Management Algorithm

If This Combination Is Medically Necessary:

Step 1: Cardiovascular Monitoring

• Obtain baseline blood pressure and heart rate before starting clonidine 1
• Take a complete medical history including family history of sudden death, repeated fainting, or arrhythmias, which would contraindicate clonidine use 1
• Monitor blood pressure regularly due to additive hypotensive effects from clonidine and aripiprazole 2

Step 2: CNS Depression Monitoring

• Monitor for excessive sedation, which can precede respiratory depression 1
• Assess fall risk, particularly if the patient is elderly 1
• Educate patient/caregivers about signs of respiratory depression 1

Step 3: Dosing Considerations

• Use the lowest effective doses of each medication 1
• If clonidine is used, start with 0.05 mg at bedtime and increase slowly, never exceeding 0.3 mg/day 1
• Consider whether all four medications are truly necessary or if some can be tapered 1

Step 4: Prioritize Medication Reduction

• If possible, taper the benzodiazepine (Valium) first, as this poses the greatest risk when combined with other CNS depressants 1
• Benzodiazepine tapering should be gradual (25% reduction every 1-2 weeks) to avoid withdrawal seizures 1
• Consider evidence-based alternatives to benzodiazepines for anxiety (e.g., cognitive behavioral therapy, antidepressants) 1

Common Pitfalls to Avoid

• Do not abruptly discontinue benzodiazepines, as this can cause seizures, delirium, and rarely death 1
• Do not dismiss cardiovascular monitoring with clonidine - bradycardia occurs in approximately 17.5% of patients 3
• Do not assume that because each medication is prescribed separately, the combination is safe - the cumulative CNS depression is the primary concern 1
• Do not overlook the enhanced hypotensive effects when aripiprazole and clonidine are combined 2

Evidence-Based Combinations That Have Been Studied

• Gabapentin and clonidine together have been studied and found effective for pain control in specific contexts (pediatric spinal surgery, diabetic neuropathy) without unique serious side effects beyond those of individual agents 4, 5
• However, these studies did not include concurrent benzodiazepines or antipsychotics 4, 5

Bottom Line

This four-drug combination significantly increases risks of sedation, respiratory depression, falls, and cardiovascular effects (hypotension, bradycardia). While not absolutely contraindicated, it requires close monitoring of vital signs, sedation level, and fall risk. The benzodiazepine (Valium) poses the greatest concern and should be tapered if clinically feasible 1. If all four medications are deemed necessary, use the lowest effective doses, monitor cardiovascular parameters closely, and educate the patient about warning signs of excessive CNS depression 1, 2.